我们已揭示少突胶质细胞系中的ErbB受体协同调控中枢髓鞘的发育和完整性，近来又以遗传标记手段发现可同时激活ErbB1/4的配体HB-EGF表达于特定脑区的神经元，尤其在大脑皮层中特异表达于各种初级和次级感觉皮层的第VI层兴奋性神经元中。HB-EGF敲除鼠出现特异性的大脑后部的皮层深层和对应的胼胝体区域髓鞘发育不良的现象。这种中枢局域性髓鞘发育不良的表型，为精神分裂症等精神疾病中的局域性白质缺陷的临床表型提供了潜在的遗传机制。前期结果提示HB-EGF以神经元源性机制调控髓鞘发育。对HB-EGF的分子机制的解析将进一步完善ErbB信号通路调控中枢髓鞘发育的配体机制。作为首次被发现的调控特定神经回路髓鞘发育的关键分子，对HB-EGF作用机制的研究将修正对泛化的中枢髓鞘调控机制的认识；而对HB-EGF敲除动物的行为学分析将对研究感觉皮层间的胼胝体交通对各种感觉相关的大脑基础功能的贡献具有重要意义。

In our past work, we have demonstrated that different ErbB receptors in oligodendroglial lineage coordinate to regulate myelin development and integrity. Recently, through a genetically labeling approach, we found that Heparin-binding EGF-like growth factor (HB-EGF), a ligand that binds both ErbB1 and ErbB4, expresses in neurons of specific brain regions. Especially in the cerebral cortex, HB-EGF expresses in excitatory neurons of layer VI in the primary and secondary sensory cortex, including somatosensory cortex, visual cortex, and auditory cortex. Intriguingly, HB-EGF-knockout mice exhibited impaired myelin formation within the location of HB-EGF-expressing neurons and correlated callosal pathways. The phenotype of focal hypomyelination in the central nervous system of HB-EGF-knockout mice is reminiscent of focal lesions observed in the white matter of schizophrenics or patients with other psychiatric disorders, providing a potential genetic evidence to such a clinical phenotype. Our preliminary work suggested that HB-EGF regulated myelin development via a neuron-derived manner. Understanding how HB-EGF works would add the ligand information to our knowledge about how ErbB signaling pathways regulate central myelination. As a first identified molecule that regulates myelin formation specifically on a certain neural circuit, investigation of HB-EGF would help to correct our existed dogma that central myelination is generally regulated. Furthermore, behavioral analyses of HB-EGF-knockout mice would provide valuable clues of how callosal communication between the bilateral cortical regions for somatosensation, vision, or audition contributes to the related basic brain functions.